chr14-20060162-A-G

Position:

• chr14-20060162-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004717.1(OR4L1):​c.118A>G​(p.Met40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,597,686 control chromosomes in the GnomAD database, including 156,739 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.44 (15310 hom., cov: 31)
  • Exomes 𝑓: 0.43 (141429 hom.)
• Consequence: OR4L1 NM_001004717.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.57

Genes affected

OR4L1 (HGNC:15356): (olfactory receptor family 4 subfamily L member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1081136E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4L1	NM_001004717.1	c.118A>G	p.Met40Val	missense_variant	1/1	ENST00000315683.1	NP_001004717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4L1	ENST00000315683.1	c.118A>G	p.Met40Val	missense_variant	1/1	6	NM_001004717.1	ENSP00000319217.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66976 AN: 151676 Hom.: 15277 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.427

GnomAD3 exomes AF: 0.469 AC: 114711 AN: 244498 Hom.: 29121 AF XY: 0.473 AC XY: 62536 AN XY: 132182

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.604

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.582

Gnomad SAS exome AF: 0.689

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.433 AC: 625908 AN: 1445892 Hom.: 141429 Cov.: 29 AF XY: 0.440 AC XY: 316406 AN XY: 719502

Gnomad4 AFR exome AF: 0.488

Gnomad4 AMR exome AF: 0.592

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.442 AC: 67066 AN: 151794 Hom.: 15310 Cov.: 31 AF XY: 0.445 AC XY: 32972 AN XY: 74156

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.430

Alfa AF: 0.416 Hom.: 33882

Bravo AF: 0.453

TwinsUK AF: 0.413 AC: 1532

ALSPAC AF: 0.421 AC: 1624

ESP6500AA AF: 0.489 AC: 2154

ESP6500EA AF: 0.403 AC: 3465

ExAC AF: 0.471 AC: 57194

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.057
DANN	Benign	0.61
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0041	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.89	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.046
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.011
ClinPred		0.018	T
GERP RS		-5.8
Varity_R		0.052
gMVP		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1958716; hg19: chr14-20528321;